Education
PhD, Pharmacy, The University of Nottingham, UK
Bachelor degree, PharmD, The University of Jordan, Jordan
Research Interests
My research interests focus on molecular and cellular mechanisms governing gene expression, cellular stress responses, and their roles in health and disease, with an emphasis on RNA biology and functional regulation of cellular processes.
Selected Publications
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Uncovering the role of RNA binding proteins in the ER stress response in pancreatic beta cells. (Manuscript submitted).
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Published abstract. R Almomani, R Wardman, C Charoensuk, T Sekaran, T Schwarzl, I Huppertz, J Whitehead, D Hodson, M Hentze, TP Herbert., April 2024. The identification of ‘secretory’ RNA-binding proteins (RBPs) provides evidence for a hitherto unknown link between gene expression and insulin exocytosis. Diabetes UK, 41(S1), 17‐19. London, UK.
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Published abstract. TP Herbert1, A Al-Bazaz, C Charoensuk, R Al-Momani, , W See, R Barnes, J Whitehead, D Boocock, April 2024. Uncovering the role of RNA binding proteins in the ER stress response in pancreatic beta cells. Diabetes UK, 41(S1), 17‐19. London, UK.
Professional Experience
Teaching Courses
- Pharmacology I (BSc.)
- Pharmacoloy II (BSc.)
- Pharmacology III (BSc.)
- Pharmacogenomics (BSc.)
- Toxicology (BSc.)
- Research methodology and Biostatistics (MSc.)
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all.
This person’s work contributes towards the following SDG(s):
Memberships
- Member of the British Pharmacological Society
- Member of the Diabetes UK
- Member of the British Biochemical Society
Uncovering the role of RNA binding proteins in the ER stress response in pancreatic beta cells
Published in: Diabetes UK Professional Conference
Apr 16, 2024
Uncovering the role of RNA binding proteins in the ER stress response in pancreatic beta cells TP Herbert1, A Al-Bazaz1, C Charoensuk1, R Al-Momani1, W See1, R Barnes1, J Whitehead2, D Boocock3 1School of Pharmacy, University of Lincoln, Lincoln, UK; 2School of Life and Environmental Sciences, University of Lincoln, Lincoln, UK; 3John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, UK Aim: Chronic ER stress is implicated in the development of beta cell dysfunction and death in diabetes. As RNA-binding proteins (RBPs) likely play an essential role in ER stress-induced changes in gene expression, the aims of this research were to identify global changes in the binding of RBPs to RNA in response to ER stress in beta cells, and then to determine the role of ER-stress-regulated RBPs in beta cell function. Methods: The mouse beta cell line, MIN6, were incubated in the presence or absence of thapsigargin, a pharmacological inducer of ER stress, and RNA bound RBPs identified using RNA interactome capture (RiC) and quantitative mass spectroscopy (SWATH-MS). Knock-down cells of selected stress-regulated RBPs were generated by shRNA. Changes in gene expression were determined by qPCR and Western blot analysis, whereas viability was assessed using Alamar blue. Results: Three hundred twenty-four RBPs were identified of which 49 were modulated by ER stress (i.e. p > 0.05 and 1.5× fold change) including the RNA helicase, Ddx3x, whose binding to mRNA was promoted by ER stress. Bioinformatic analysis of published CLIP data for Ddx3x revealed common Ddx3x target mRNAs associated with ER stress and the unfolded protein response (UPR). knock-down of Ddx3x in MIN6 cells reduced the expression of defined target mRNAs in response to ER stress, including ATF4 and CHoP, and delayed ER stress-induced cell death. Conclusion: Our results provide evidence that ER stress-regulated RBPs play an important role in the execution of the UPR and thus beta cell fate. Support Information: This work is supported by a Diabetes UK studentship.
The identification of ‘secretory’ RNA-binding proteins (RBPs) provides evidence for a hitherto unknown link between gene expression and insulin exocytosis
Published in: Diabetes UK Professional Conference
Apr 16, 2024
The identification of ‘secretory’ RNA-binding proteins (RBPs) provides evidence for a hitherto unknown link between gene expression and insulin exocytosis R Almomani1, R Wardman1, C Charoensuk1, T Sekaran2, T Schwarzl2, I Huppertz2, J Whitehead1, D Hodson3, M Hentze2, TP Herbert1 1School of Pharmacy and Life Sciences, University of Lincoln, Lincoln, UK; 2European Molecular Biology Laboratory, Heidelberg, Germany; 3Medical Sciences Division, University of Oxford, Oxford, UK Aims: The aims of the study were to identify global changes in the binding of RBPs to RNA in response to glucose in pancreatic beta cells, and then to determine the role of selected glucose-regulated RBPs in beta cell function. Methods: Experiments were performed using the mouse beta cell line, MIN6. Global identification of RBPs was determined using RNA interactome capture (RIC) and quantitative mass spectroscopy (SWATH-MS). Enhanced crosslinking immunoprecipitation (eCLIP) was used to identify RNAs bound to RBPs, and electrophoretic mobility shift assays (EMSA) and RNA immunoprecipitation (RIP) were used to confirm these findings. Results: Three hundred ninety-eight RBPs were identified of which the binding of 59 to RNAs were significantly modulated by glucose. Ontological analysis revealed an enrichment of non-canonical RBPs associated with membrane trafficking and exocytosis, which we have named ‘secretory-RBPs’. These included N-ethylmaleimide sensitive fusion protein (NSF) and vesicle-associated membrane protein 2 (VAMP2), whose binding to RNA was stimulated by glucose, driven by an increase in intracellular calcium. RNAs bound to NSF and VAMP2 were identified using eCLIP which demonstrated an enrichment of mRNAs encoding proteins associated with exocytosis, which was confirmed using EMSA and RIP. Conclusion: An increase in calcium promotes the coordinated recruitment of a subset of mRNAs to secretory-RBPs, which we hypothesise modulates their localisation and/or expression, thus revealing a hitherto unknown link between gene expression and insulin exocytosis. Support Information: This work was/is supported by the Diabetes Research and Wellness Foundation, the European Molecular Biology Organisation, the Leverhulme Trust, and Diabetes UK.